title: Hybrid compounds as new Bcr/Abl inhibitors.
abstract: A series of 2,4-disubstituted thiazole derivatives were designed and synthesized as new Bcr/Abl inhibitors by hybriding the structural moieties from FDA approved imatinib, nilotinib and dasatinib. The new inhibitors strongly suppressed the activity of Bcr/Abl kinase and potently inhibited the proliferation of K562 and KU812 leukemia cancer cells. Compound 4i displayed comparable potency with that of nilotinib in both biochemical kinase assay and cancer cell growth inhibition assay. These inhibitors might serve as lead compounds for further developing new anticancer drugs.
authors.affiliation: Key Laboratory of Regenerative Biology and Institute of Chemical Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, No 190, Kaiyuan Avenue, Science Park, Guangzhou 510530, China.
authors.forename: Deping
authors.initials: D
authors.lastname: Wang
authors.forename: Zhang
authors.initials: Z
authors.lastname: Zhang
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Lu
authors.forename: Yubing
authors.initials: Y
authors.lastname: Feng
authors.forename: Kun
authors.initials: K
authors.lastname: Luo
authors.forename: Jirong
authors.initials: J
authors.lastname: Gan
authors.forename: Liu
authors.initials: L
authors.lastname: Yingxue
authors.forename: Junting
authors.initials: J
authors.lastname: Wan
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.forename: Fengxiang
authors.initials: F
authors.lastname: Zhang
authors.forename: Zhengchao
authors.initials: Z
authors.lastname: Tu
authors.forename: Qian
authors.initials: Q
authors.lastname: Cai
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Ren
authors.forename: Ke
authors.initials: K
authors.lastname: Ding
mesh_terms: D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors*; D006801:Humans; D007938:Leukemia / Q000473:pathology; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D013844:Thiazoles; D016044:Fusion Proteins, bcr-abl